COMPLEMENT C5B-9 INCREASES PLASMINOGEN BINDING AND ACTIVATION ON HUMAN ENDOTHELIAL-CELLS

Deposition of the terminal complement proteins (C5b-9) on human endoth elial cells can result in cell lysis or nonlytic alterations of cell f unction including procoagulant responses. Because regulation of fibrin olysis is a central endothelial function and because C9 contains a car boxyl-terminal lysine similar to other proteins that bind and facilita te activation of plasminogen (PG), the effects of complement injury on PG binding and activation on these cells were investigated. Activatio n of complement through deposition of C5b67 complexes on endothelial c ells resulted in a small increase (approximate to 20%) in PG binding. Incorporation of C8 into C5b-8 resulted in no further increase in bind ing; however, specific I-125-PG binding was increased by approximate t o 100% after C5b-9 deposition. Moreover, PG was found to bind specific ally to C7 and C9. The PG bound to endothelial cells after C5b-9 depos ition was readily activated by tissue-type plasminogen activator (TPA) . In a cell-free system, complement C9 and a synthetic peptide compose d of the 20 carboxyl-terminal amino acids of C9 enhanced PG activation by TPA. Removal of the carboxyl-terminal lysine of C9 abolished the e nhancement of PG activation without diminishing PG binding. We conclud e that membrane C9 may comprise a binding site for PG and serve to enh ance activation of this zymogen by TPA. These findings suggest that im mune injury to the endothelium may enhance both the fibrin-generating and fibrinolytic capacity of the vessel wall.